This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hegele, R. A. Articles by Anderson, C. M. Search for Related Content PubMed PubMed Citation Articles by Hegele, R. A. Articles by Anderson, C. M.

LMNA R482Q Mutation in Partial Lipodystrophy Associated with Reduced Plasma Leptin Concentration¹

John P. Robarts Research Institute, London, Ontario, Canada N6A 5K8

Address all correspondence and requests for reprints to: Dr. Robert A. Hegele, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406–100 Perth Drive, London, Ontario, Canada N6A 5K8. E-mail: robert.hegele{at}rri.on.ca

Mutations in LMNA, which encodes lamins A and C, have been found in patients with autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed the relationship between plasma leptin and the rare LMNA R482Q mutation in 23 adult FPLD subjects compared with 25 adult family controls with normal LMNA in an extended Canadian FPLD kindred. We found that the LMNA Q482/R482 genotype was a significant determinant of plasma leptin, the ratio of plasma leptin to body mass index (BMI), plasma insulin, and plasma C peptide (P = 0.015, P = 0.0007, P = 0.0004, and P < 0.0001, respectively), but not BMI (P = 0.67). Family members who were heterozygous for LMNA Q482/R482 had significantly lower plasma leptin and leptin:BMI ratio than unaffected R482/R482 homozygotes. Fasting plasma concentrations of insulin and C peptide were both significantly higher in LMNA Q482/R482 heterozygotes than in R482/R482 homozygotes. Multivariate regression analysis revealed that the LMNA R482Q genotype accounted for 40.9%, 48.2%, 86.9%, and 81.0%, respectively, of the attributable variation in log leptin, leptin:BMI ratio, log insulin, and log C peptide (P = 0.013, P = 0.0007, P = 0.0002 and P < 0.0001, respectively). The results indicate that a rare FPLD mutation in LMNA determines the plasma leptin concentration. It remains to be established whether the reduction in leptin results from the reduced adipose tissue mass in FPLD or from another subcellular effect of mutant LMNA. It also remains to be established whether the insulin resistance in FPLD is a consequence of the reduced plasma leptin or of another functional change resulting from mutant LMNA.

This article has been cited by other articles:

				R. Cortese, F. Eckhardt, M. Volleth, M. Wehnert, U. Koelsch, P. Wieacker, and T. Brune The retinol acid receptor B gene is hypermethylated in patients with familial partial lipodystrophy J. Mol. Endocrinol., June 1, 2007; 38(6): 663 - 671. [Abstract] [Full Text] [PDF]

				L. Wegner, G. Andersen, T. Sparso, N. Grarup, C. Glumer, K. Borch-Johnsen, T. Jorgensen, T. Hansen, and O. Pedersen Common Variation in LMNA Increases Susceptibility to Type 2 Diabetes and Associates With Elevated Fasting Glycemia and Estimates of Body Fat and Height in the General Population: Studies of 7,495 Danish Whites Diabetes, March 1, 2007; 56(3): 694 - 698. [Abstract] [Full Text] [PDF]

				V. T. K. Chow and M. C. Phoon MEASUREMENT OF SERUM LEPTIN CONCENTRATIONS IN UNIVERSITY UNDERGRADUATES BY COMPETITIVE ELISA REVEALS CORRELATIONS WITH BODY MASS INDEX AND SEX Advan Physiol Educ, June 1, 2003; 27(2): 70 - 77. [Abstract] [Full Text] [PDF]

				K. L. Herbst, L. R. Tannock, S. S. Deeb, J. Q. Purnell, J. D. Brunzell, and A. Chait Kobberling Type of Familial Partial Lipodystrophy: An underrecognized syndrome Diabetes Care, June 1, 2003; 26(6): 1819 - 1824. [Abstract] [Full Text] [PDF]

				M. K. S. Leow, C. L. Addy, and C. S. Mantzoros Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1961 - 1976. [Full Text] [PDF]

				R. A. Hegele, M. E. Kraw, M. R. Ban, B. A. Miskie, M. W. Huff, and H. Cao Elevated Serum C-Reactive Protein and Free Fatty Acids Among Nondiabetic Carriers of Missense Mutations in the Gene Encoding Lamin A/C (LMNA) With Partial Lipodystrophy Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 111 - 116. [Abstract] [Full Text] [PDF]

				C. Grunfeld Leptin and the Immunosuppression of Malnutrition J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3038 - 3039. [Full Text] [PDF]